title: A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death.
abstract: BACKGROUND
  Ex vivo heart perfusion (EVHP) has been proposed as a means to facilitate the resuscitation of donor hearts after cardiocirculatory death (DCD) and increase the donor pool. However, the current approach to clinical EVHP may exacerbate myocardial injury and impair function after transplant. Therefore, we sought to determine if a cardioprotective EVHP strategy that eliminates myocardial exposure to hypothermic hyperkalemia cardioplegia and minimizes cold ischemia could facilitate successful DCD heart transplantation.
  
  
  METHODS
  Anesthetized pigs sustained a hypoxic cardiac arrest and a 15-minute warm ischemic standoff period. Strategy 1 hearts (S1, n = 9) underwent initial reperfusion with a cold hyperkalemic cardioplegia, normothermic EVHP, and transplantation after a cold hyperkalemic cardioplegic arrest (current EVHP strategy). Strategy 2 hearts (S2, n = 8) underwent initial reperfusion with a tepid adenosine-lidocaine cardioplegia, normothermic EVHP, and transplantation with continuous myocardial perfusion (cardioprotective EVHP strategy).
  
  
  RESULTS
  At completion of EVHP, S2 hearts exhibited less weight gain (9.7 ± 6.7 [S2] vs 21.2 ± 6.7 [S1] g/hour, p = 0.008) and less troponin-I release into the coronary sinus effluent (4.2 ± 1.3 [S2] vs 6.3 ± 1.5 [S1] ng/ml; p = 0.014). Mass spectrometry analysis of oxidized pleural in post-transplant myocardium revealed less oxidative stress in S2 hearts. At 30 minutes after wean from cardiopulmonary bypass, post-transplant systolic (pre-load recruitable stroke work: 33.5 ± 1.3 [S2] vs 19.7 ± 10.9 [S1], p = 0.043) and diastolic (isovolumic relaxation constant: 42.9 ± 6.7 [S2] vs 65.2 ± 21.1 [S1], p = 0.020) function were superior in S2 hearts.
  
  
  CONCLUSIONS
  In this experimental model of DCD, an EVHP strategy using initial reperfusion with a tepid adenosine-lidocaine cardioplegia and continuous myocardial perfusion minimizes myocardial injury and improves short-term post-transplant function compared with the current EVHP strategy using cold hyperkalemic cardioplegia before organ procurement and transplantation.
authors.affiliation: Cardiac Sciences Program, University of Manitoba, St Boniface Hospital, Winnipeg, Manitoba, Canada.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: White
authors.forename: Ayyaz
authors.initials: A
authors.lastname: Ali
authors.forename: Devin
authors.initials: D
authors.lastname: Hasanally
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: Mundt
authors.forename: Matthew
authors.initials: M
authors.lastname: Lytwyn
authors.forename: Simon
authors.initials: S
authors.lastname: Colah
authors.forename: Julianne
authors.initials: J
authors.lastname: Klein
authors.forename: Amir
authors.initials: A
authors.lastname: Ravandi
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Arora
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Lee
authors.forename: Larry
authors.initials: L
authors.lastname: Hryshko
authors.forename: Stephen
authors.initials: S
authors.lastname: Large
authors.forename: Ganghong
authors.initials: G
authors.lastname: Tian
authors.forename: Darren H
authors.initials: DH
authors.lastname: Freed
mesh_terms: D000241:Adenosine / Q000627:therapeutic use*; D000818:Animals; D003643:Death; D005260:Female; D006324:Heart Arrest, Induced; D016027:Heart Transplantation; D008012:Lidocaine / Q000627:therapeutic use*; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion; D013552:Swine
chemical_list: D008012:Lidocaine; D000241:Adenosine